ERBB2 and neoplasm: Moderate HER2(2+) status is defined as having 500,000 detectable HER2 receptors on the cell surface, which are required to activate the essential intracellular HER2 pathway to drive tumor growth and invasion (22).In contrast, a relatively small proportion of HER2 2+ patients had a negative prognostic impact with low level of HER2, scoring 1+ or 2+ on IHC but negative on FISH, suggesting that HER2 IHC 1+ may have similar biological behavior with HER2 IHC 2+ that could adversely affect prognosis.